Constructing a Novel Signature Based on Immune-Related lncRNA to Improve Prognosis Prediction of Cervical Squamous Cell Carcinoma Patients.

Xuefeng Lv,Yingying Yuan,Dongchun Qin,Lu Liu,Mengle Peng,Pengxiang Li,Huifang Jin

doi:10.1007/s43032-022-00851-z

Abstract

We downloaded gene expression data, clinical data, and somatic mutation data of cervical squamous cell carcinoma (CSCC) patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Predictive lncRNAs were screened using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and risk scores were calculated for each patient according to the expression levels of lncRNAs and regression coefficients to establish a risk model that could be a novel signature. We assessed the correlation between immune infiltration status, chemotherapeutics sensitivity, immune checkpoint proteins (ICP), and the signature. Therefore, we selected 11 immune-related lncRNAs (WWC2,AS2, STXBP5.AS1, ERICH6.AS1, USP30.AS1, LINC02073, RBAKDN, IL21R.AS1, LINC02078, DLEU1, LINC00426, BOLA3.AS1) to construct the risk model. Patients who were in the high-risk group had a shorter survival time than those in the low-risk group (p < 0.001). Risk scores in the signature were negatively correlated with macrophage M1, macrophage M2, and T cell CD8 + ; what's more, T cell CD8 + was higher in the low-risk group. The expression levels of ICP such as PD-L1, PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 were substantially higher in the low-risk group. For chemotherapeutic agents, high-risk scores were associated with higher half-inhibitory concentrations (IC50) of cisplatin. These findings suggested that the risk model can be a novel signature for predicting CSCC patients' prognosis, and it also can be used to formulate clinical treatment plans for CSCC patients.

Highlights

Cervical squamous cell carcinoma is the fourth dominant cause of cancer-related deaths in women worldwide, accounting for 80– 85% of all cervical cancer diagnoses.[1, 2]
In addition to participating in the tumor microenvironment, Long non-coding RNAs (lncRNAs) can affect the response to immunotherapy[15], which is rarely reported in cervical squamous cell carcinoma (CSCC) patients
Data analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases produced 1,081 differentially expressed lncRNAs (DElncRNAs), of which 224 were DEirlncRNAs (Figure. 2a) and 11 of those were related to prognosis in CSCC samples

Summary

Introduction

Cervical squamous cell carcinoma is the fourth dominant cause of cancer-related deaths in women worldwide, accounting for 80– 85% of all cervical cancer diagnoses.[1, 2]. With human papillomavirus (HPV) vaccination and early-stage screening, the incidence rate of CSCC has decreased significantly. Radiotherapy, and chemotherapy have been commonly used for cervical cancer patients, but the 5-year survival rate is still not satisfactory because of advanced stage, relapse, metastasis, and drug resistance[3,4,5]. LncRNA CamK-A was found to be highly expressed in various human cancers and could regulate Ca2+-signaling-mediated tumor microenvironment remodeling[12]. In colorectal cancer cells, overexpression of HLA-FAS1 could repress miR-375 and promote the expression of PFN1, further parting macrophages toward M2 phenotype and exacerbating tumorigenesis[13]. In addition to participating in the tumor microenvironment, lncRNAs can affect the response to immunotherapy[15], which is rarely reported in CSCC patients

Methods

Results

Conclusion